High-throughput synthesis of metallic nanoparticles

ABSTRACT

This invention relates to cost-effective methods for synthesizing metallic nanoparticles in high yield using non-dendrimeric branched polymeric templates, such as branched polyethyleneimine. This invention also provides a high-throughput apparatus for synthesizing metallic nanoparticles under conditions that produce less waste than conventional nanoparticle synthesis methods. Also provided are metallic nanoparticles and multi-metallic nanoparticle compositions made by methods and high-throughput apparatus of the invention.

RELATED APPLICATIONS

This application claims priority to provisional application 62/510,104,filed on May 23, 2017, which is herein incorporated in its entirety byreference.

GOVERNMENT LICENSE RIGHTS

This invention was made with government support under grant 00039202awarded by the NSF under the Center for Sustainable Nanotechnology. Thegovernment has certain rights in the invention.

FIELD OF THE INVENTION

This invention relates to methods and reactors for producing metallicnanoparticles in high yield. The invention also relates to metallicnanoparticles prepared by the methods and reactors of the invention.

BACKGROUND OF THE INVENTION

Nanoparticles are small particles of matter with a diameter typically inthe range of 1 to 100 nanometers. Nanoparticles are useful in manytechnological areas including medicine (e.g., drug delivery), energygeneration (e.g., solar cells, fuel cells, etc.), and energy storage(e.g., batteries). Nanoparticles can be comprised of many differenttypes of materials, including polymers, ceramics, metals, and proteins,to name just a few.

Nanoparticles can be synthesized in a variety of ways. For example, ingas phase synthesis, nanoparticles are formed by initially evaporatingthe constituent materials and then causing nucleation and growth of thenanoparticles, typically in an inert gas environment. Nanoparticle mayalso be formed using sol-gel processing, a wet-chemical technique inwhich certain chemical additives in a solution form small particles,resulting in a composition with the consistency of a gel. Theseparticles may be isolated using precipitation and hydrothermaltreatments. If desired, nanoparticles also may be formed from sol-gelsusing cavitation processing, which involves the creation and release ofgas bubbles in the sol-gel. Nanoparticles may also be formed usingdendrimers (a highly symmetrical synthetic polymer with a tree-likestructure) as host template that stabilizes the nanoparticles againstaggregation. Yet another method of forming nanoparticles involves atechnique known as chemical vapor condensation, in which vapor phaseprecursors are brought into hot-wall chemical reactors under conditionsthat promote reaction to form nanoparticles. Nanoparticles may also beformed by sonochemical processing, which involves subjecting theconstituent material to sudden pressure and temperature changes to formthe nanoparticles. Grinding methods, such as high-energy ball milling,can also be used to create nanoparticles from larger particles.

While several methods for producing nanoparticles currently exist, thesemethods suffer from some substantial drawbacks. For example, some of themethods produce dangerous chemical waste as a by-product, which poses asignificant environmental risk. Others are not cost-effective becausethey require the input of large amounts of energy, costly equipment, orcostly reagents. For example, dendrimer-mediated production ofnanoparticles is exceedingly expensive, making commercialization of suchprocesses economically unfeasible. In addition, while some conventionalmethods are capable of producing nanoparticles, they may be unable toprevent undesirable aggregation or oxidation of the nanoparticles (e.g.,high energy ball milling). Reproducibility and the ability to producewell-defined nanoparticles with characteristic shapes and sizes are alsodifficult to achieve with conventional methods for producingnanoparticles.

In view of these limitations, it would be advantageous to develop a newmethod of producing nanoparticles in high yield and with well-definedshapes and sizes. It would also be advantageous to develop an apparatusfor making such nanoparticles in a cost-effective, environmentallyfriendly way.

SUMMARY OF THE INVENTION

The present invention relates to a novel flow reactor for the synthesisof Polyethyleneimine coated nanoparticles (“PEI-coated nanoparticles”).The inventors compared the resulting nanoparticles (“NPs”) to thosesynthesized through traditional batch synthesis with the Polyamidoamine(“PAMAM”) dendrimer. PEI was chosen as the capping agent because it is alow-cost alternative to the PAMAM dendrimer with known affinity forcopper. In the flow reactor, metal salt solutions are premixed with PEIand subsequently reduced to metal zero via chemical reduction, whileunder steady flow conditions. However, immediate oxidation is observeddue to exposure to ambient conditions, producing Cu NPs with a nativeoxide layer. The inventors provide comparative characterization ofsmall-scale synthesized PAMAM- and large-scale synthesized PEI-cappedcopper nanoparticles using x-ray diffraction (XRD), transmissionelectron microscopy (TEM), and UV-vis spectroscopy to demonstrate theunexpected benefits of the flow reactors of the invention.

Although many advances have been made in the batch synthesis processingof metallic Cu and Cu-based nanoparticles, the inability to controlagglomeration and size distribution during the scale-up process is acommon drawback that remains unsolved. By using a flow reactor of theinvention combined with the chemical reduction process and PEI as thechelating and stabilizing agent, nanoparticles with well-defined sizesand shapes can be achieved at the gram scale without significantaggregation. The flow reactor design is capable of high-throughputproduction of CuO nanoparticles with spherical morphology.

In the flow reactor, a peristaltic pump is used to drive fluids throughmillimeter-diameter tubing at flow rates that range between 0.4 mL/minand 85 mL/min. A flow rate of 20 mL/min was used to produce PEI-cappedCu nanoparticles. It should be noted that the flow rate used in thisreactor will likely depend on the type of metal salt solution andreaction type chosen. The flow reactors of the invention provide amethod of fabricating nanoparticles where the growth solution usedcontains only the polymer ligand and the metal salt (no ligand or seednanoparticles are necessary). Subsequently, NaBH₄ (reducing agent) orultraviolet light can be used to produce Cu-based NPs.

The invention exploits the ion-pair exchange chemistry that serves asthe basis for PAMAM-dendrimer methods. Rather than using the expensivePAMAM dendrimer, the inventors used the secondary amine groups presentin PEI to create the ligand-to-metal-charge transfer exchange to drivechemical reduction of the metal salt to form nanoparticles. That is, inthis reaction, coordination chemistry through ligand substitution isused to form bonds around the aqua-copper ions to form a Cu—NH bond.When a premixed aqueous solution of PEI and aqueous solution of coppersalt was introduced into the flow reactor with various residence times(the amount of time the solution spends flowing in the tubing after itmeets at the t-mixer), copper oxide NPs are formed. Upon exiting theflow reactor, the PEI-coated particles were freeze-dried to promotelong-term stability until characterization or use.

Accordingly, in one aspect, the invention provides a method ofsynthesizing metallic nanoparticles. The method comprises providing afirst flow stream comprising an aqueous solution comprising ions of atransition metal and a branched polymeric template, wherein the branchedpolymeric template is not a dendrimer. The first flow stream issubjected to a reducing agent to reduce the ions of the transition metalto form metallic nanoparticles within the branched polymeric template.Optionally, the metallic nanoparticles may be separated from thebranched polymeric template.

In another aspect, the invention provides an apparatus for synthesizingmetallic nanoparticles. The apparatus comprises a first device forproviding a first flow stream comprising an aqueous solution comprisingions of a transition metal and a branched polymeric template, whereinthe branched polymeric template is not a dendrimer. The apparatusfurther comprises a second device for providing a reducing agent thatreduces the ions of the transition metal in the first flow stream,thereby forming metallic nanoparticles.

In yet another aspect, the invention provides a nanoparticlecomposition. The nanoparticle composition comprises a branched polymerictemplate, and a plurality of metallic nanoparticles disposed within thepolymeric template.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: A schematic illustration of an apparatus for producing metallicnanoparticles according to one embodiment of the invention.

FIG. 2: A schematic illustration of an apparatus for producing metallicnanoparticles according to another embodiment of the invention.

FIG. 3: A schematic diagram of an exemplary flow reactor set-up forsynthesizing copper nanoparticles using polyethyeleneimine as a branchedpolymeric template.

FIG. 4: A schematic diagram of another exemplary flow reactor set-up forsynthesizing copper nanoparticles using polyethyeleneimine (PEI) as abranched polymeric template.

FIG. 5A: UV-vis spectra of copper nanoparticles in PEI during synthesisand after aging for one month.

FIG. 5B: Typical UV-vis spectra revealing the extinction spectra for thecopper salt (Cu(NO₃)₂.2.5H₂O) and copper oxide nanoparticles formedafter the reduction process has occurred under flow reactor conditions.

FIG. 6A: a photograph of copper nanoparticles taken immediately afterfreeze-drying;

FIG. 6B: photograph of copper nanoparticles taken after one month ofaging.

FIG. 7A: Cu(2p) XPS and Cu(L₃M₄₅M₄₅) Auger transitions observed fordifferent Cu-containing samples. From bottom to top; the as-receivedCuNPs; the CuNPs after argon sputtering (60 minutes at 10×10⁻³ Pa, 4kV); a Cu metal foil standard; a copper(I) oxide standard sputtered forlmin to remove Cu(II) species (10×10⁻³ Pa, 4 kV). Sputtering studies ofthe copper nanoparticles, taken as a function of sputtering time andcompared with a copper (0) foil. Left panel: Cu 2p XPS spectra; Rightpanel: Cu (L₃M₄₅M₄₅) Auger electron spectra.

FIG. 7B: XRD of PEI-coated copper oxide nanoparticles and simulatedCu(OH)₂, NaBH₄, Cu metal and different forms of simulated copper oxides(CuO and Cu₂O).

FIG. 8: X-ray diffraction pattern of copper nanoparticles prepared inaccordance with the methods of the invention.

FIG. 9: FIG. 9(a) TEM image of Cu nanoparticles prepared usingconvention PAMAM G4-mediated synthesis; FIG. 9(b) size distributionprofile of Cu nanoparticles prepared using convention PAMAM G4-mediatedsynthesis; FIG. 9(c) TEM image of Cu nanoparticles made using a PEIbranched polymeric template in accordance with the invention; FIG. 9(d)size distribution profile of Cu nanoparticles prepared using a PEItemplate according to one embodiment of the invention.

FIG. 10: XRD of Dendrimer-encapsulated zero-valent copper synthesis viathe chemical reduction method.

DETAILED DESCRIPTION OF THE INVENTION

In one aspect, this invention provides a method of producing metallicnanoparticles in a branched polymeric template. Among other things, thisinvention recognizes that non-dendrimer, branched polymeric templatesare suitable for cost-effective production of metallic nanoparticles inhigh-yield using the reactors of the invention. By using the methods andreactors disclosed herein, the cost of forming metallic nanoparticlescan be over 250 times cheaper than the cost of forming metallicnanoparticles using conventional, dendrimer-based methods. Moreover, themethods and reactors of the invention produce less waste compared to theconventional, dendrimer-based methods and reactors.

The metallic nanoparticles of the invention find use in a variety ofdifferent technologies. For example, copper-based nanoparticles can beused as additives in bioactive coatings. Nickel-based nanoparticles finduse in catalysis. Cobalt-based nanoparticles are useful for informationstorage and also energy storage. Titanium- and zirconium-basednanoparticles find use as coatings and additives.

In one aspect, this invention provides a method of synthesizing metallicnanoparticles. The method comprises providing a first flow streamcomprising an aqueous salt solution comprising ions of a transitionmetal and a branched polymeric template. The first flow stream issubjected to a reducing agent that causes the formation of metallicnanoparticles within the branched polymeric template. Using the methodsand reactors disclosed herein, gram-scale quantities of nanoparticlescan be obtained efficiently. For example, in certain preferredembodiments, the residence time of the first flow stream within thereactor (i.e., from the time when a portion of the first flow stream isintroduced to the time when the formation of the metallic nanoparticlesfrom that portion is substantially complete) is in the range of about 3to about 15 minutes, about 4 to about 12 minutes, about 5 to about 10minutes, or about 6 to about 8 minutes. After the metallic nanoparticlesare formed, they are optionally separated from the branched polymerictemplate.

The term “metallic nanoparticle” as used herein refers to a particlethat is substantially comprised of one or more transition metals andthat has a maximum dimension in the range of 1 to 100 nanometers. Whilethe metallic nanoparticles of the invention are preferably substantiallyspherical, certain embodiments of this invention contemplate metallicnanoparticles that are not substantially spherical. Non-sphericalmetallic nanoparticles may be produced by using branched polymerictemplates with suitable morphologies to promote anisotropic growth,thereby leading to metallic particles with non-spherical shapes.Alternatively, non-spherical metallic nanoparticles may be produced byadding capping reagents that preferentially bind to certain crystallinefaces of the metallic nanoparticles as they form. In this way, growth incertain crystalline directions is kinetically limited, leading toanisotropic growth and non-spherical metallic nanoparticles. In certainpreferred embodiments, the invention provides methods for formingmetallic nanoparticle compositions in which the metallic nanoparticlesare substantially uniform in size. In this context, the term“substantially uniform” means that the magnitude of the standarddeviation of the particle size is 25% or less of the average particlesize.

The metallic nanoparticles contemplated by the invention may compriseone or more types of metal. In general, suitable metals are typicallytransition metals, non-limiting examples of which include iron, cobalt,rhodium, iridium, nickel, palladium, platinum; copper, silver, gold,zirconium, and titanium. When the metallic nanoparticles comprise two ormore different metals, the distribution of the metals within themetallic nanoparticles may be controlled by varying the processingconditions. As described herein, the metallic nanoparticles of theinvention are formed within a branched polymeric template by exposingthe branched polymeric template to a salt solution containing transitionmetal ions and then reducing the transition metal ions to form themetallic nanoparticles within the branched polymeric template. Thus,metallic nanoparticles comprising a random distribution of two or moremetals may be formed by adding different types of transition metal saltsto the salt solution before combining the salt solution with thebranched polymeric templates and reducing the metal ions to formmetallic nanoparticles. In an alternative embodiment, the differenttypes of metals in the metallic nanoparticles may be arranged inconcentric layers by sequentially exposing the branched polymerictemplates to a series of salt solutions, each comprising a differenttype of transition metal ion, and reducing the transition metal ions inthe particular solution before exposing the branched polymeric templatesto the next salt solution. Hybrid approaches comprising single metallayers in combination with multi-metallic layers are also expresslycontemplated by the invention.

The salt solutions containing the transition metal ions that are to bereduced in order to form the metallic nanoparticles of the invention aretypically aqueous solutions that contain one or more dissolvedtransition metal salts. In general, any transition metal salt that issoluble in an aqueous solution may be used, with transition metalhalides, nitrates, sulfates, and phosphates being preferred. Preferably,the salt solutions contain transition metal ions present at aconcentration in the range of about 1 μM to 200 mM, more preferably inthe range of 1 μM to 20 mM, and most preferably in the range of about 1μM to about 1 mM. Salt solutions containing two or more differentsoluble transition metal salts are also contemplated by the invention.

As used herein, the term “branched polymeric template” refers to acarbon-based, branched polymeric structure that is not a dendrimer andthat comprises heteroatoms capable of coordinating with a metal atom,such as a transition metal atom. Non-limiting examples of suchheteroatoms include nitrogen, oxygen, phosphorus, and sulfur, withnitrogen being particularly preferred. By way of example, in certainpreferred embodiments, the branched polymeric template is apolyalkyleneimine, with polyethyleneimine and polypropyleneimine beingparticularly preferred. Examples of oxygen-containing branched polymerictemplates include branched polyethers and branched polyesters. Examplesof sulfur-containing branched polymeric templates include branchedthioesters and branched polysulfides. In general, the size of thebranched polymeric templates is not particularly limited and can be anysize in which permits the diffusion of metal ions therein and extractionof the metallic nanoparticles once they are fully formed. Non-limitingexamples of suitable branched polymeric templates include those thathave a number average molecular mass (M_(n)) in the range of about 5,000to about 15,000, about 7,000 to about 13,000, about 8,000 to about12,000 and most preferably, about 10,000.

As described herein, the metallic nanoparticles according to theinvention typically are formed by reducing the transition metal ions inthe metal salt solutions, thereby causing the formation of metallicnanoparticles in the branched polymeric templates. Without wishing to belimited by theory, it is believed that the transition metal ions areinitially chelated to the heteroatoms of the branched polymerictemplate, and that these chelation sites act as nucleation centers forthe growth of the metallic nanoparticles. Thus, in preferredembodiments, the metal salt solutions are combined with the branchedpolymeric templates before exposure to a reducing agent. In preferredembodiments, the metallic nanoparticles are produced by a continuousflow process. For example, the metal salt and the branched polymerictemplate may be premixed in a solution which is delivered as a firstflow stream that is subsequently subjected to a reducing agent.Alternatively, a flow stream comprising a metal salt solution may becombined with a flow stream comprising the branched polymeric templatein order to form a first flow stream that is subsequently subjected to areducing agent. The invention also contemplates other embodimentswherein a flow stream comprising transition metal ions is exposed to areactor in which the branched polymeric template is dispersed on ahigh-surface-area support, such as mesoporous silica. This promotesmixing and efficient chelation of the transition metal ions by theheteroatoms in the branched polymeric template. Subsequently, thetransition metal ion/branched polymeric template composition can beexposed to a reducing agent as described herein.

One of the methods contemplated by the invention for reducing thetransition metal ions in the salt solutions involves exposing thetransition metal ions to a chemical reducing agent. For example, incertain embodiments, the chemical reducing agent is a metal hydride,non-limiting examples of which include sodium borohydride, lithiumaluminum hydride, and lithium triethylborohydride. When the reducingagent is a chemical reducing agent, it is preferable to select abranched polymer template that does not contain any functional groupsthat would react with the chemical reducing agent, in order to avoid thepossibility of undesirable side reactions. For instance, when thechemical reducing agent is a metal hydride, it is preferable that thebranched polymeric template does not contain any ester groups (e.g.,polyester), which could undergo competing reduction reactions involvingthe carbonyl moiety of the ester groups and the hydride. Thus, when thechemical reducing agent is a metal hydride, preferred branched polymerictemplates include polyalkyleneimines, such as polyethyleneimine (PEI)and polypropyleneimine (PPI), for example. In preferred embodiments, thechemical reducing agent is introduced into the reactor in a second flowstream that is combined with the first flow stream comprising the metalsalt solution.

In addition to chemical reducing agents, the invention also specificallycontemplates forming metallic nanoparticles in a branched polymerictemplate by photoreducing transition metal ions in a salt solution,typically after the salt solution has been combined with the branchedpolymeric template. In certain embodiments, the photoreduction isaccomplished by irradiating the first flow stream comprising thetransition-metal-ion-containing salt solution and the branched polymerictemplate with ultraviolet light. Suitable ultraviolet light sourcesinclude any that (1) produce ultraviolet radiation with a wavelengththat causes photoreduction reactions of transition metal ions to occur;and (2) has a sufficient photon flux to cause the growth of metallicnanoparticles at a reasonable rate. By way of example, ultraviolet lightsources contemplated by the invention include mercury lamps, xenon arclamps, mercury-xenon arc lamps, deuterium arc lamps, metal halide arclamps, and tungsten-halogen incandescent lamps. In a particularlypreferred embodiment, the ultraviolet light source is a monochromaticsource that provides ultraviolet light at a wavelength of 254 nm. Inother embodiments, the photoreduction reaction is accomplished usingvisible light in connection with a photocatalytic material that iscapable of acting as an electron source for the photoreduction reaction.Non-limiting examples of such photocatalytic materials include certainmetal oxides (e.g., TiO) as well as certain types of chemical dyes(e.g., erythrosin).

After the metallic nanoparticles have been formed within the branchedpolymeric template, they may be recovered from the branched polymerictemplate, if desired. Recovery may be accomplished using a variety ofdifferent techniques. For example, recovery of the metallicnanoparticles from a branched polymeric template may be accomplished byusing a ligand exchange reaction to functionalize the metallicnanoparticles, thereby facilitating the extraction of the metallicnanoparticles from the branched polymeric template. In one exemplaryembodiment, metallic nanoparticles are functionalized by addingdodecanethiol to the metallic nanoparticle/branched polymeric templatemixture. Without wishing to be limited by theory, it is believed thatthe thiol groups of the added dodecanethiol bind to the surfaces of themetallic nanoparticles, rendering them more mobile and able to diffuseout of the branched polymeric template. If desired, the metallicnanoparticles may be recovered using diafiltration, a membrane basedseparation method that can separate the metallic nanoparticles from thebranched polymeric template. Alternatively, the branched polymerictemplate may be removed by subjecting the metallic nanoparticle/branchedpolymeric template composition, after drying, to an oxygen plasma. Theoxygen plasma selectively etches away the branched polymeric templateand any other organic material, leaving behind the metallicnanoparticles.

The invention also provides an apparatus for manufacturing the metallicnanoparticles according to the invention. Broadly speaking, theapparatus comprises a first device for delivering an aqueous solutioncomprising ions of a transition metal and a branched polymeric templatein a first flow stream. The apparatus further comprises a second devicefor reducing the transition metal ions of the salt solutions. In certainembodiments, the second device provides a second flow stream comprisinga chemical reducing agent that mixes (preferably under conditions ofcontinuous flow) to cause formation of the metallic nanoparticles withinthe branched polymeric template. Moreover, instead of delivering achemical reducing agent, the second device may be a light source that iscapable of causing the photoreduction of the transition metal ions inthe salt solution that have been combined with the branched polymerictemplate. If desired, the apparatus may comprise additional purificationunits (e.g., a diafiltration unit) that optionally may be fluidlyconnected to the reactor. In preferred embodiments, the apparatus forproducing metallic nanoparticles according to the invention is acontinuous flow reactor.

FIG. 1 shows a schematic diagram of an apparatus 100 for producingmetallic nanoparticles according to one exemplary implementation of theinvention. In FIG. 1, device 110 is fluidly connected to reactor 120.Device 110 contains a salt solution of a transition metal salt and, whenneeded, delivers the salt solution to reactor 120 via its fluidconnection to reactor 120. In certain embodiments, reactor 120 comprisesa branched polymeric template, such as polyethyleneimine (PEI). Incertain embodiments, the branched polymeric template is highly dispersedwithin reactor 120. For example, the branched polymeric template may bepresent in reactor 120 as a high-surface-area powder that ispre-dissolved in an aqueous medium. As another non-limiting example, thebranched polymeric template in reactor 120 may be physically mixed withmesoporous silica that provides a high-surface-area substrate to supportthe growth of metallic nanoparticles in the branched polymeric template.Alternatively, if desired, the branched polymeric template may bepremixed with the salt solution before the salt solution is admittedinto reactor 120, either by a batch mixing process or by a bringingtogether in a continuous flow process a flow stream comprising thetransition metal ions and a flow stream comprising the branchedpolymeric template. In the embodiment shown in FIG. 1, reactor 120 isequipped with an optical port 125 that admits ultraviolet light 135 fromUV light source 130 into reactor 120. The UV light 135 emanating from UVlight source 130 contains radiation at wavelengths suitable for causingthe photoreduction of the transition metal ions in the solution fromdevice 110. Thus, when the solution from device 110 is admitted intoreactor 120, UV light 135 may be admitted into reactor 120 to causephotoreduction of the transition metal ions in the solution. Apparatus100 further comprises separation unit 140 which is used to separate thebranched polymeric template from the metallic nanoparticles containedtherein using, for example, a ligand exchange reaction, diafiltration,or an oxygen plasma. The metallic nanoparticles that are recovered fromseparation unit 140 may be further purified by purification unit 150,which may comprise different filtering, washing, and drying steps, asneeded.

FIG. 2 shows a schematic diagram of an apparatus 200 for producingmetallic nanoparticles according to another exemplary implementation ofthe invention. In FIG. 2, device 210 is fluidly connected to reactor220. Device 210 contains a salt solution of a transition metal salt and,when needed, delivers the salt solution to reactor 220 via its fluidconnection to reactor 220. Similar to the case for reactor 120 in FIG.1, in certain embodiments, reactor 220 comprises a branched polymerictemplate, such as polyethyleneimine (PEI). The branched polymerictemplate (e.g., PEI) is preferably highly dispersed within reactor 220(e.g., pre-dissolved in an aqueous medium or physically mixed withmesoporous silica that provides a high-surface-area substrate to supportthe growth of metallic nanoparticles in the branched polymerictemplate). Alternatively, if desired, the branched polymeric templatemay be premixed with the salt solution of device 210 before the saltsolution is admitted into reactor 220, either by a batch mixing processor by a bringing together in a continuous flow process a flow streamcomprising the transition metal ions and a flow stream comprising thebranched polymeric template. Apparatus 200 further comprises device 230which is fluidly connected to reactor 220. Device 230 contains asolution containing a chemical reducing agent (e.g., sodium borohydride)and, when needed, delivers the salt solution to reactor 220 via itsfluid connection to reactor 220. In the embodiment shown in FIG. 2,device 210 and device 230 are fluidly connected via junction 235. Whenthe salt solution from device 210 and the chemical reducing agent fromdevice 230 are combined with the branched polymeric template in reactor220, metal nanoparticles will form within the branched polymerictemplate as a result of the chemical reduction of the transition metalions in salt solution from device 210. In certain embodiments, the saltsolution and the chemical reducing agent are admitted sequentially intoreactor 220. However, if desired, a solution comprising a transitionmetal salt and a branched polymeric template and a solution comprisingthe chemical reducing agent can be premixed via junction 235 before theyare admitted into reactor 220.

EXAMPLES Example 1: Synthesis of Metal Nanoparticles in a Branched PEITemplate and in a PAMAM Dendrimer

Branched polyethyleneimine, H(NHCH₂CH₂)NH₂, average M_(w)˜25,000 by LS,average M_(n)˜10,000 by GPC and generation four (G4) PAMAM dendrimerwere purchased from Sigma Aldrich. Copper(II) nitratehemi(pentahydrate), Cu(NO₃)₂.2.5 H₂O was used as the metal source.Deionized water was used as the solvent and sodium borohydride (NaBH₄)was used as the reducing agent. All chemicals were of analytical reagentgrade and purchased from Sigma Aldrich Chemical Company. Stock solutionsof polyethyleneimine (PEI) at 0.5 weight percent and 1 weight percent(wt %) and micromolar concentration of dendrimer were prepared. (To formthese solutions, PEI was weighed and dissolved in 500 mL of deionizedwater, and the solution was heated to 50° C. for 30 minutes.). A 0.2 Msolution of the copper salt was prepared by dissolving 5.815 g of theas-received copper salt into 125 mL of deionized water and used as theCu metal source.

Using ultraviolet-visible spectroscopy (UV-vis), absorbance spectra werecollected for the polyethylenimine metal salt solution and for thecomplexation of Polyethylenimine-copper solution (PEI-(Cu²⁺)_(x) beforechemical reduction. All absorbance measurements were carried out using aHewlett-Packard HP 8453 UV-visible spectrophotometer equipped with a 1.0cm optical path length quartz crystal cuvette. The wavelength range ofanalysis was 250-800 nm.

X-ray photoelectron spectra (20sw, 59.7eVPE, 0.125eVstep) were collectedon a PHI 5600 XPS system equipped with a Mg Kα X-ray (1253.6 eV) source(Physical Electronics, Chanhassen, Minn.). Powdered black/blue Cu NPswere dusted onto double sided carbon tape, initial photoelectron spectrawere collected before and after sputtering with an Ion Gun at 10×10⁻³ PaAr⁺ with at a constant current of +0.7 uA. XPS Spectra were measuredafter 1, 5, 15, 30 and 60 mins of sputtering. XPS (100 sweeps, 59.7 eVpass energy, 0.125 eV/step). 99.99% copper foil, (Strem Chemicals) Ar+sputtered for 15 min, was utilized as a standard for metallic copper.Similarly, a copper(I) oxide sample, sputtered for one minute to removeCu(II) oxide that formed at the surface was used as a copper (I) oxidereference.

X-ray diffraction (XRD) measurements were used to determine thecrystallographic structure of the Polyethylenimine-coated Cu NPs. X-raydiffraction analyses were carried out using a Rigaku D/MAX 2200 X-raydiffractometer with a diffracted beam graphite monochromator using Cu Kαradiation. Analysis was performed from 0° to 80° of 20 angle at a rateof 5 degrees per minute and a sample width of 0.02. The data werecollected and peaks were analyzed using PDF data base of Joint Committeeon Powder Diffraction Standards (JCPDS).

Transmission electron microscopy (TEM) was used to image the Cu NPsproduced by the batch process, dendrimer-mediated Cu NPs and the newmethod of nanoparticle production, fluidic flow PEI-synthesized Cu NPs.Before imaging, Cu NPs were dispersed in Milli-Q water in a one-dramvial (15 mm width×45 mm length) and diluted with Milli-Q water until thecolor of the resulting dispersion was not apparent looking through thevial but was apparent looking along the length of the vial. Note thatthe dendrimer-mediated Cu NP solution exhibited a brown/yellow hue andPEI-synthesized Cu NP solution exhibited a blue hue. A 6 μL drop of eachsuspension was deposited on 200 mesh copper TEM grids with Formvar andcarbon supports (Ted Pella Inc., Redding, Calif.). The grids wereallowed to dry in ambient conditions with a protective cover to preventcontamination by dust. Images were collected using a Tecnai T12transmission electron microscope with an operating voltage of 120 kV atvarious magnifications. Images were processed in Image J. The line toolwas used to determine the diameter of the Cu NPs formed by the dendrimerand PEI processing methods; more than 600 individual nanoparticles weresized in each condition.

Example 2: Synthesis of Dendrimer-Mediated Copper Nanoparticles

A standard chelation and chemical reduction procedure was used. Inshort, the prepared dendrimer and copper salt solutions were mixed witha 55 mol equivalent of Cu(NO₃)₂.2.5H₂O to dendrimer with continuousstirring. Subsequently, a complex solution of dendrimer and metal ionsDen-(Cu²⁺)_(X) where X=55 mole ratio was formed. After 15 minutes ofcontinuous stirring, the addition of 10-fold excess of freshly preparedaqueous reducing agent “NaBH₄” was added in a drop-wise manner to thecomplex solution to produce zero-valent Cu nanoparticles via chemicalreduction. All nanoparticle growth experiments were carried out under aN₂ atmosphere to prevent oxidation as the Cu nanoparticles formed.

The reactor is composed of multiple modular commercially availablecomponents. In this setup, the fluid flow is driven by the peristalticpump and mixing of each component (salt solutions, reducing agent, andhosting agent—PEI) occurs in the reactor cell. Although our CuOnanoparticles are freeze-dried at the end of the production process toincrease shelf-life, the reactor flow diagram above also features anintegrated purification system wherein ligand-exchange chemistry can beused as an additional attachment to the reactor system to create ahigh-throughput approach for nanoparticle purification.

FIG. 3 shows a highly schematic diagram of an apparatus 300 that wasused for producing metallic nanoparticles in accordance with oneexemplary embodiment of the invention. In FIG. 3, apparatus 300 is aflow reactor that included first device 310 that was configured todeliver salt solutions of nickel, copper, and/or cobalt. Apparatus 300further comprised a second device 320, which was configured to deliver achemical reducing agent (here, sodium borohydride NaBH₄). Apparatus 300further comprised device 330, which was configured to deliverpolyethyeleneimine (PEI), a branched polymeric template. The saltsolution(s), chemical reducing agent, and PEI were combined viaperistaltic pump 340 to produce metallic nanoparticle solution 350. Theperistaltic pump 340 was capable of mixing several solutions via at-mixer setup during the nanoparticle formation process. In thisexample, the peristaltic pump 340 was a Thomas 3386 Mini Variable SpeedTubing Pump with a 0.4 to 85 mL/min flowrate control range. Polyvinyltubing with a 6.35 mm internal diameter and a t-mixer with an internaldiameter of 4.32 mm were used to transport and mix both thePEI-(Cu²⁺)_(x) solution and reducing agent in concert and, subsequently,the solution was collected into the flow reactor cell. The flow rate wascontrolled to manipulate the residence time of the premixedPEI-(Cu²⁺)_(x) solution and reducing agent flowing through the reactiontubing. During particle formation, residence times of 3-10 minutes fromthe point of mixing to the point of entering the reactor cell resultedin substantially uniform Cu nanoparticles. From this example, it wasobserved that when the PEI-(Cu²⁺)_(x) solutions were premixed in thisflow reactor the required residence time to produce nanoparticles wassignificantly reduced.

The reactor may be composed of multiple modular commercially availablecomponents. In this setup, the fluid flow can be driven by theperistaltic pump and mixing of each component (salt solutions, reducingagent, and hosting agent—PEI) occurs in the reactor cell. Although CuOnanoparticles can be freeze-dried at the end of the production processto increase shelf-life, the reactor flow diagram above also features anintegrated purification system wherein ligand-exchange chemistry can beused as an additional attachment to the reactor system to create ahigh-throughput approach for nanoparticle purification.

Example 3: Gram-Scale Synthesis of PEI-Coated Cu Nanoparticles

Gram-scale synthesis of PEI-coated Cu nanoparticles was accomplishedusing apparatus 400 shown schematically in FIG. 4. Broadly speaking,apparatus 400 comprised device 410 which was configured to combine apre-mixed solution of a Cu⁺² salt and PEI with a chemical reducing agent430 via T-mixer 435. The mixture was pumped via peristaltic pump 420 toproduce Cu nanoparticles coated with PEI, which was recovered incontainer 440. The polyethyleneimine (concentration 0.5 wt % to 1 wt %)was purchased and used as the stabilizer and capping agents and as theion-pair exchanged medium (branched polymeric template). Micromolarconcentrations (between 1 mM to 20. mM) of the copper salt solutionswere prepared and mixed with the 0.5 wt % to 1.0 wt % PEI solution topromote formation of a complex of polyethyleneimine and metal ions(PEI-(Cu²⁺)_(X) where X=0.5 or 1 wt %). Under pumping conditions toprovide a flow rate of 20 mL/min, the chemical reducing agent (freshlyprepared 1.0 M NaBH₄ reducing agent) and the complexed PEI-(Cu²⁺)_(X)solutions were added to the reaction cell at a constant rate of flow viaT-mixer 435 as shown in FIG. 4. A flow rate of 20.0 (or in certain casesa flow rate of 23.0) mL/min was empirically determined to achieveoptimal Cu nanoparticle monodispersity in this reactor. To enhance thelifetime of the stable PEI-coated Cu nanoparticles, the Cu nanoparticleswere freeze-dried and stored in test tubes at temperatures below −25° C.to minimize aggregation caused by the nanoparticle-to-nanoparticleinteractions that initiate aggregation in batch reactor processes. Theyield of Cu nanoparticles made in accordance with these procedures was>90%.

Mass measurements were conducted to determine the total amount ofnanoparticles produced at the end of the flow-reactor runtime. Based onthese mass measurements made after freeze-drying of the resultingPEI-encapsulated copper oxide nanoparticles, gram-scale synthesis of CuOnanoparticles can be achieved through continuous flow mixing of thecomplex solution and reducing agent at micro- and nanomolarconcentrations or by increasing the concentration to millimolar toreduce the amount solution needed and reaction runtime. Since PEI isused to stabilize the Cu nanoparticles as they are synthesized, higherconcentrated precursor solutions (ca. 0.20 mM) can be used to producegram-scale Cu nanoparticle without the occurrence of NP aggregation dueto the mitigation of metal-to-metal attraction. That is, increasing theconcentration of the precursor solution does not lead to aggregation ofthe formed copper oxide nanoparticles. In the lower concentration cases,1000.00 mL of PEI-(Cu²⁺) at 0.5 wt % or 1.0 wt % is mixed with equalvolumes of reducing agent and flowed at a rate of 23 mL/min with anin-residence runtime of 50 minutes. Similar conditions are used athigher concentrations (>1M), however, in this case, only 125 mL of thePEI-(Cu²⁺) solution mixed with an approximate total in residence time of6 minutes.

Based on the foregoing results and on extrapolating calculations usingabsorbance spectroscopy and Beers Law, the invention recognizes thatgram-scale synthesis of Cu nanoparticles can be achieved throughcontinuous flow mixing of the complex solution and reducing agent atmicro- and nanomolar concentrations or by increasing the concentrationto millimolar to reduce the amount solution needed and reaction runtime.In particular, since PEI is used to stabilize the Cu nanoparticles asthey are synthesized, super-concentrated precursor solutions (ca. 0.20mM) can be used to produce gram-scale Cu nanoparticle without theoccurrence of aggregation due to the direct interruption of themetal-to-metal attraction.

In addition, the invention recognizes that when dilute solutions areused, Cu nanoparticles may be formed by increasing the residence time.Thus, in certain embodiments, the residence time is about 45, 50, 55,60, 65, 70, 75, or even 90 minutes. When using more concentratedsolutions (about 1 mM to 200 mM), only 125 mL of the PEI-(Cu²⁺) solutionneeds to be mixed with the chemical reducing agent, and the approximatetotal in residence time is only 6 minutes. Thus, using more concentratedsalt solutions can result in faster metallic nanoparticle formation.

Example 4: UV-Visible and X-Ray Photoelectron SpectroscopicCharacterization of Flow Reactor-Synthesized Cu Nanoparticles

Copper and copper oxide nanoparticles exhibit UV-vis absorbance peaks ataround 590 nm and 390 nm, respectively. FIG. 5A provides UV-vis spectrataken under ambient atmospheric conditions during the formation of theCu nanoparticles and one month after the Cu nanoparticles were formed inaccordance with Example 1. In each case, the spectra were recorded withthe Cu nanoparticles in an aqueous solution. The UV-vis spectra revealinformation pertaining to the process by which the Cu nanoparticles areformed and their stability upon reduction to aggregation; these datasuggest minimal aggregation over the timescale of one month. As can beobserved, under the chelation and chemical reduction method, once thePEI-(Cu⁺²)_(x) has been reduced, copper nanoparticles are formed. Theinitial reduction absorbance spectrum shows a broad, low intensitylocalized surface plasmon resonance (LSPR) peak at approximately 598 nmwhich is indicative of the formation of Cu nanoparticles with no nativeoxide layer (FIG. 5A). Typically, Cu nanoparticles with diameters around4 nm exhibit strong broadening of the plasmon band. Furthermore, as moreCu nanoparticles are formed, the UV-vis absorbance peak observed ataround 598 nm typically increases in intensity. This is the directresult of more copper nanoparticles being formed as the flow reactioncontinues. The absence of any peaks at 390 nm for UV-vis measurementtaken at the initial and final stages of the flow process indicates thatno native oxide layer was formed. This shows that gram-scale Cunanoparticles have been synthesized without any modification of surfacecharacteristics due to oxidation.

FIG. 5B shows UV-Vis spectra pertaining to the process by which the Cunanoparticles are formed. In this figure, a spectrum of the copper saltand of the reduced copper nanoparticles were analyzed to determine if Cuor CuO nanoparticles are being formed. As can be observed, under thechelation and chemical reduction method, once the PEI-(Cu2+)x has beenreduced, copper oxide nanoparticles are formed. The initial absorbanceof the copper salt (ca. 808 nm) shifts dramatically after chelation withthe amines of the PEI and subsequent reduction via sodium borohydride.That is, the extinction spectrum shows a broad, low intensity peak atapproximately 608 nm and another peak at 275 nm that is indicative ofthe formation of CuxO (i.e., Cu2O and CuO) NPs.

Aging studies were performed to determine the stability of thePEI-coated Cu nanoparticles. After storing the Cu nanoparticles for onemonth in an aqueous suspension, a slight shift in the LSPR to longerwavelengths (ca. 641 nm) was observed, indicating that the PEI-coated Cunanoparticles had begun to oxidize. This was further verified by avisual observation of the one-month-old Cu nanoparticle freeze-driedpowder, which showed a slight blue tint indicating the presence ofoxidized Cu nanoparticles. (See FIG. 6). The oxidation was expectedsince the PEI-coated nanoparticles were stored in water under normalatmospheric conditions during the freeze-drying process. FIGS. 6A and 6Bshow photographs of the PEI-coated CuO NPs immediately afterfreeze-drying (FIG. 6A) and after exposure to ambient conditions for onemonth (FIG. 6B). Apparently, macroscale physical changes of the freshlyprepared PEI-coated CuO NP powder are observed when compared to its1-month aged counterpart. As can be observed, obvious color and texturechanges are evident in the aged sample. To determine the exact impact ofthis change on the physical and chemical state of the PEI-coagted CuONPs, further investigations were conducted using XPS and XRD.

X-ray photoelectron spectroscopy (XPS) studies were performed to confirmthat the nanoreactor-synthesized Cu nanoparticles gradually oxidize uponexposure to ambient conditions. XPS analysis of the Cu nanoparticles(prepared in accordance with Example 1) revealed the presence ofsignificant concentrations of boron (11%), carbon (35%), nitrogen,oxygen (38%), and sodium (3%) with only a small (1%) Cu concentration.The boron and sodium can be ascribed to residual NaBH₄ used in thenanoparticle synthesis while the carbon, nitrogen, and most of theoxygen are a reflection of the PEI polymer adsorbed onto the coppernanoparticle surface. A detailed scan of the Cu 2p region (lower lefthand spectra in FIG. 7A) showed the presence of Cu(II) species, asevidenced by the presence of shake-up peaks at ≈9 eV higher than theprincipal Cu 2p^(1/2) and 2p^(3/2) peaks. After 60 minutes of argon ionsputtering, however, the Cu(II) shake-up peaks had diminished and theCu(2p) and Cu (L₃M₄₅M₄₅) auger line shape had changed to resemble thoseof metallic copper foil (compare the Cu(2p) and Cu(L₃M₄₅M₄₅) regions inthe upper two spectra in FIG. 7A. Thus, the XPS data are consistent withcopper metal nanoparticles having a thin copper oxide shell at thesurface and a copper metal core. Moreover, a comparison of the Cu(2p)and Cu(L₃M₄₅M₄₅) Auger transitions with those observed from a sputtercleaned Cu(0) metal foil and a Cu(I) oxide reference (uppermost two setsof spectra in FIG. 7A) indicates that the surface of the Cu NPs iscomposed exclusively of Cu(II)O. Upon sputtering the Cu NPs, the signalsassociated with the organic and inorganic species (C, N, O and B)greatly decreased and the intensity of the elemental Cu peakscorrespondingly increased. FIG. 7B shows that argon sputtering producedsignificant changes in the Cu(2p) and Cu (L₃M₄₅M₄₅) auger line shapes.Unfortunately, Cu(II)O is known to be extremely susceptible to ion beaminduced reduction, compromising the ability of Ar⁺ sputtering to provideunambiguous diagnostic information on the depth dependent composition ofcopper oxides. However, since the surface of these Cu NPs represents alarge fraction of the material, the XPS data indicates that the majorityof the copper atoms are present as Cu(II)O.

FIG. 7B provides XRD data of PEI-coated copper oxide nanoparticles andsimulated Cu(OH)₂, NaBH₄, Cu metal and different forms of simulatedcopper oxides (CuO and Cu₂O). Note that the peak matches from thesimulated XRD spectra indicates that both CuO and Cu₂O are formed uponreduction of the PEI-Cu⁺² complex. The slight mismatch in peak positionfor some of simulated data when compared to the experimental data isinsignificant and can be attributed to a mismatch in the exactsimulation settings (e.g., temperature).

Example 5: XRD and TEM Characterization of Flow Reactor-Synthesized CuNanoparticles

XRD and TEM analyses were performed to determine the crystal structure,size, and shape of the PEI-coated copper oxide NPs produced using theflow reactor. FIG. 7B shows the typical XRD pattern for the PEI-coatedcopper oxide NPs along with simulated XRD spectra for several relevantpossible products; these simulated patterns were made usingCrystalDiffract software based on structural parameters from theCrystallography Open Database. It is well-documented in the literaturethat XRD peaks observed at diffraction angles (2θ) of 43.6°, 50.8°, and74.4° correspond to (111), (200), (220) reflections of elemental Cu(0)in a face-centered cubic structure. These peaks are not observed in ourXRD spectrum. However, the simulations using Crystal-Diffract confirmthe UV-vis and XPS data showing that copper oxide is formed after thereduction of the PEI-Cu⁺² complex with sodium borohydride. The presenceof Cu₂O is confirmed by the observance of XRD peaks at 29.68°, 42.6°,and 61.76° 2″ and corresponds to (110), (200), (220), and (311)diffraction planes, respectively, and the presence of CuO is confirmedby the observance of XRD peaks at 32.5°, 35.5°, 38.7°, 48.7°, 63.4°, and66.2° corresponding to (110), (002), (111), (202), (113), and (311)diffraction planes, respectively. As can be observed in FIG. 9, thesimulated spectra for Cu₂O and CuO show XRD peak positions that matchwell with the expected XRD peak positions in our experimental XRDspectrum. That is, the simulated XRD patterns for both copper oxidescorrespond well with the pattern shown for the experimental datapresented in FIG. 7B. Furthermore, this supports the XPS observationsthat the majority of the copper nanoparticles is present as CuO whengrown in our system and freeze-dried. The peak at around 26.6° 2″ can beattributed to the silicon substrate used to hold the sample during theXRD analysis. Thus, we conclude that Cu NPs grown in our system areprimarily in the oxidized (Cu₂O and CuO) form.

XRD and XPS measurements of PEI-coated copper oxide NPs that were storedfor 1 month in aqueous suspension show similar results for copper oxideformation.

A represented TEM micrograph of the Cu nanoparticles produced underdendrimer-encapsulation templating is shown in FIG. 9A and itscorresponding particle size histogram in FIG. 9B. The size of Cu NPsreported here exceed the typical average size (ca. 1.8 nm) that has beenreported in the literature when Cu²⁺ ions are chelated using a OHterminated, fourth-generation (G4) dendrimer and chemically reducedusing excess NaBH₄. A G4 dendrimer has an internal diameter around 4.5nm which limits the overall average size of the Cu NP that forms withinthe protected cavity. Hence, in this case, observance of Cunanoparticles with average sizes that exceeds the diameter reported foran OH terminated dendrimer is inconceivable based on the physicalapproach used to explain the Cu nanoparticle formation process reportedby Crooks and coworkers. Nanoparticles formed on this scale with ageneration 4 dendrimer is often reported with the amine (NH₂) terminateddendrimer structure where the pH has been controlled (pH>3.5) toinitiate growth on the peripheral via protonation of the external aminegroups. In this case, instead of formation of dendrimer-encapsulated Cu(intra-dendrimer) nanoparticles, nanoparticles bind at the terminalamines of the dendrimer structure and are stabilized by thedendrimer-to-dendrimer interactions (inter-dendrimer). This explanationis ruled out in this case since OH terminated dendrimers are used toconduct this study. One other viable solution is that there is acompeting reaction taken place yielding two sets of nanoparticle sizeregimes. Crook et al. reported that when using the OH terminateddendrimer Cu²⁺ ions are present both inside the dendrimer and ashydrated ions in solution when excess sodium borohydride is used as thereducing agent. After reduction, it is reported that these excess Cu²⁺ions form dark precipitates with 9±4 nm in average diameter. Thus, inthis case, the larger sized nanoparticles formed due to the excess Cu²⁺ions available in the solution have skewed the overall average deducedfrom the TEM images.

A representative TEM micrograph of the PEI-coated copper nanoparticlesis shown in FIG. 9C. This TEM micrograph, along with the correspondingsize distribution profiles provided in FIG. 9D, show that the Cunanoparticles produced under the flow reactor conditions of Example 1exhibit high uniformity in their shape and size. The prominent shapeobserved here is spherical in nature with an average diameter of 4.8±1.4nm. See FIG. 9D. The diameter of the nanoparticles are further confirmedby using the Debye-Scherer equation when based on the FWHM of the (111)XRD reflection plane revealed an estimated average particle size of 5 nmthat is in good agreement with the observed average size as revealed byTEM imaging. Hence, the XRD and TEM analyses indicate thatPEI-stabilization within the flow reactor facilitates production ofsingle-phased (fcc phase only), zero-valent Cu nanoparticles withspherical geometries and diameters as small as 3.4 nm during thereaction process. However, it is noted that since these nanoparticlesare synthesized in ambient conditions, the oxidation of the formed Cuparticles occur in less than a month.

Example 6: Comparative Example with Dendrimer Template

The chemical reduction method using the PEI-mediated synthesis approachcan be used to scale up copper oxide NP production to the gram scalewithout sacrificing NP quality. Thus, we compared CuO particles producedusing the reactor to those produced by traditional dendrimer-basedsynthesis (Table I). More specifically, in this section, we provide acomparison of the Cu nanoparticles produced by both methods todemonstrate the effectiveness of the flow system in producing similarwell-defined, spherical shaped CuO NPs with scaled up quantities. Thisexample compares the copper nanoparticles synthesized using a PEItemplate in accordance with the invention with copper nanoparticlesformed using a conventional PAMAM G4 dendrimer. Table 1 provides acomparison of certain properties of the Cu nanoparticles produced inaccordance with the invention with the properties of coppernanoparticles produced by using a conventional PAMAM G4 dendrimer.

TABLE 1 Tabulated data comparing Cu NPs synthesized using the flowreactor and dendrimer-mediated process. Source PAMAM DendrimerPolyethylenimine, PEI Structure Type Branch (G4) Branch ParticleDiameter 4.13 ± 1.26 nm 4.80 ± 1.14 nm Geometry Spherical SphericalCrystal Phase FCC FCC Stability (aggregation 150 days >150 daysprevention) Scalability No Yes

FIGS. 9(a) and 9(c) are plan view TEM images of copper nanoparticlesproduced by conventional PAMAM-mediated synthesis (FIG. 9(a)) and byusing PEI as a branched polymer template in accordance with theinvention (FIG. 9(c)). Both methods produced copper nanoparticles withsmall average diameters, as indicated by the corresponding sizedistribution profiles (see FIG. 9(b), corresponding to thePAMAM-mediated synthesis and FIG. 9(d), corresponding to thePEI-mediated synthesis according to the invention). In addition, the TEMmicrographs show that in both cases, the copper nanoparticles havespherical geometries. In the case of traditional synthesis with thePAMAM dendrimer, the Cu ions were coordinated with the internal tertiaryamine groups and are subsequently reduced as zero valent CU (see FIG.10) in the internal cavities of the dendrimer, providing control overthe particle size as aggregation is prevented by dendrimerencapsulation. That is, the metal-to-metal affinity that leads tonanoparticle aggregation was mitigated by the physical entrapment of thenanoparticles inside the cavity structure of the dendrimer oncechemically reduced. Since the dendrimer controls nanoparticleaggregation using cavity entrapment, direct control of the particle sizewas achieved by controlling of the ratio of dendrimer-to-Cu salt and thecharacteristics of the dendrimer template. In addition, as confirmed inour earlier literature reports on the oxidation ofdendrimer-encapsulated Ni(0) NPs, the dendrimer only protects theencapsulated NP from surface oxidation for less than 24 hours. That is,the number of reduced Cu atoms that makeup one copper nanoparticle wasdirectly controlled through the dendrimer-to-Cu salt ratio. Furthermore,higher generations of the PAMAM dendrimer experience overcrowding at theperiphery due to interdigitation of the branching units that provides anincreased number of possible internal coordination sites for the Cu⁺²ions to form an ion-pair exchange. This drawback limits the use ofhigher generation dendrimers to scale up the production of Cunanoparticles to the gram scale due to the lack of necessary internalamido group ability to coordinate with available Cu⁺² atoms. Being morespecific, the overcrowding at the periphery of the dendrimer directlyinhibits the penetration of Cu⁺² ions, therefore, limiting thescalability of the Cu nanoparticles using this dendrimer-mediatedmethod. In addition, earlier literature reports on the oxidation ofdendrimer-encapsulated Ni(0) nanoparticles showed that the dendrimeronly protects the encapsulated nanoparticles from oxidation for lessthan 24 hours.

Unlike the batch process used in the dendrimer-mediated method ofsynthesizing copper nanoparticles, the flow reactor method describedherein allowed the complexed PEI-(Cu⁺²)_(x) solution to react with achemical reducing agent in a dynamic environment. The present method isadvantageous because it allows for direct control over the amount ofreducing agent being exposed to the complex solution and, thus,providing some level of control over the rate of nucleation of the Cunanoparticles and host molecule coating process. With introduction ofthe PEI branched polymeric template, the Cu nanoparticles produced inthis flow reactor exhibited stability against aggregation for longertime periods when compared to the dendrimer-encapsulated Cu NPs, seeTable I. Furthermore, the combination of the coating process andintroduced flow mixing of the reducing agent allowed for scalability ofthe as-synthesized Cu nanoparticle to gram amounts without anysignificant aggregation.

From the foregoing description, one of ordinary skill in the art caneasily ascertain the essential characteristics of the instant invention,and without departing from the spirit and scope thereof, can makevarious changes and/or modifications of the invention to adapt it tovarious usages and conditions. As such, these changes and/ormodifications are properly, equitably and intended to be, within thefull range of equivalence of the following claims.

What is claimed is:
 1. A method of synthesizing metallic nanoparticles,the method comprising providing a first flow stream comprising anaqueous salt solution comprising ions of a transition metal and abranched polymeric template, wherein the branched polymeric template isnot a dendrimer; subjecting the first flow stream to a reducing agent toreduce the ions of the transition metal to form metallic nanoparticleswithin the branched polymeric template; and optionally separating themetallic nanoparticles from the branched polymeric template.
 2. Themethod according to claim 1, wherein the branched polymeric templatecomprises a branched polymer selected from the group consisting ofpolyalkyleneimine, polyester, polyether, thioester, and polysulfidepolymers.
 3. The method according to claim 2, wherein the branchedpolymeric template is a polyalkyleneimine.
 4. The method of claim 3,wherein the branched polyalkyleneimine is polyethyleneimine.
 5. Themethod according to claim 1, wherein the aqueous salt solution isprepared by dissolving at least one transition metal halide, nitrate,sulfate, or phosphate in water.
 6. The method according to claim 1,wherein the nanoparticles comprise one or more metals selected from thegroup consisting of iron, cobalt, rhodium, iridium, nickel, palladium,platinum; copper, silver, gold, zirconium, and titanium.
 7. The methodaccording to claim 1, wherein the first flow stream is obtained bycombining a flow stream comprising a metal salt solution with a flowstream comprising the branched polymeric template.
 8. The methodaccording to claim 1, wherein the step of subjecting the first stream toa reducing agent comprises combining the first flow stream with a secondflow stream comprising a chemical reducing agent.
 9. The methodaccording to claim 8, wherein the chemical reducing agent is selectedfrom the group consisting of sodium borohydride, lithium aluminumhydride, and lithium triethylborohydride.
 10. The method according toclaim 1, wherein the metallic nanoparticles have a median diameter inthe range of 1 to 10 nm.
 11. The method according to claim 1, whereinthe step of subjecting the first flow stream to a reducing agentcomprises photochemically reducing the ions of the transition metal inthe first flow stream.
 12. The method according to claim 8, wherein theions of the transition metal are photochemically reduced usingultraviolet light.
 13. The method according to claim 9, wherein theultraviolet light has a wavelength of 254 nm.
 14. The method accordingto claim 1, wherein the step of optionally separating the metallicnanoparticles from the branched polyalkyleneimine template comprises aligand exchange reaction that liberates the metallic nanoparticles fromthe branched polyalkyleneimine template.
 15. The method according toclaim 1, wherein the ligand exchange reaction comprises exposing themetal nanoparticles in the branched polyalkyleneimine template to analkanethiol.
 16. An apparatus for synthesizing metallic nanoparticles,the apparatus comprising a first device for providing a first flowstream comprising an aqueous salt solution comprising ions of atransition metal and a branched polymeric template, wherein the branchedpolymeric template is not a dendrimer; a second device for providing areducing agent that reduces the ions of the transition metal in thefirst flow stream.
 17. The apparatus according to claim 16, wherein thereducing agent is a second flow stream comprising a chemical reducingagent, and wherein the second device is configured to mix the secondflow stream with the first flow stream, thereby causing the formation ofmetallic nanoparticles within the branched polymeric template.
 18. Theapparatus according to claim 17, wherein the chemical reducing agent isa metal hydride.
 19. The apparatus according to claim 18, wherein themetal hydride is selected from the group consisting of sodiumborohydride, lithium aluminum hydride, and lithium triethylborohydride.20. The apparatus according to claim 16, wherein the reducing agentphotochemically reduces the ions of the transition metal.
 21. Theapparatus according to claim 20, wherein the second device comprises anultraviolet light source.